Combined Endoscopic Transpapillary Biopsy and Exfoliative Cytology for the Diagnosis of Bile Duct Cancer

Background/Aims: In the management of patients with extrahepatic bile duct carcinoma, histologic diagnosis is crucial to determine therapeutic modalities, to predict their outcomes, and to avoid an unnecessary operation. Though various methods were developed, none of them yielded satisfactory results. A combination of those methods was reported to yield superior sensitivity and specificity to a single method. To evaluate the diagnostic efficacy, endoscopic transpapillary biopsy (ETPB) and exfoliative bile aspiration cytology (BAC) was performed in 40 patients with extrahepatic bile duct carcinoma. Methods: After visualization of the biliary tree and the lesion by endoscopic retrograde cholangiopancreatography (ERCP), ETPB (n=40) and BAC (n=28) was done in one session with or without endoscopic sphincterotomy (EST) and the results of two methods were analyzed. Results: The final diagnoses were made by surgical pathology and by clinical follow-ups of more than a year. The locations of the 40 bile duct carcinomas were in the upper area in 25, the middle in 14 and the lower in 1. ETPB was performed in all patients and BAC in 28 patients. The overall sensitivity of the ETPB was 65.0% (26/40). According to the morphology and location, the sensitivity of ETPB was 65.6% (11/32) for sclerotic, 60.0% (3/5) for papillary, and 66.7% (2/3) for the protruding type, and 68.0% (17/25) for the upper bile duct lesion, 64.3% (9/14) for the middle, and 0% (0/1) for the lower. The overall sensitivity of the BAC was 71.4% (20/28). According to the morphology and location, the sensitivity of BAC was 80.0% (16/20) for sclerotic, 20% (1/5) for papillary, and 100% (3/3) for the protruding type, and 82.4% (14/17) for the upper bile duct lesion and 54.5% (6/11) for the middle bile duct lesion. When the two tests were combined, the sensitivity rose to 96.4% (27/28). Conclusions: A combination of ETPB and BAC is useful in making a histologic diagnosis in patients with bile duct carcinoma.ope

Late Periampullary Metastasis of Renal Cell Carcinoma

Metastases to pancreas or duodenum are rarely occurring event. At autopsy, the pancreas has been found to be the site of metastases in approximately 2% of patients with malignant tumors that had originated most commonly from primary tumors located in breast, lung, and kidney. The natural history of renal cell carcinoma has been the subject of intensive study, yet its behavior remains unpredictable and poorly understood. Renal cell carcinoma may remain stable for long periods of time without growing or metastasizing, has the second highest spontaneous regression rate of all solid tumors, and metastases may develop many years after removal of the primary lesion. In patients with pancreatic mass, it is important to differentiate a secondary pancreatic tumor from primary one because satisfactory survival can be expected after surgical excision of secondary pancreatic tumor, especially when the primary tumor is renal cell carcinoma. Recently magnetic resonance image was reported to be useful in differentiating primary from secondary pancreatic tumor originated from kidney. We present a case of resectable solitary pancreatic and duodenal metastasis from renal cell carcinoma presenting as gastrointestinal bleed.ope

Delivery of Photosensitizers for Photodynamic Therapy

Photodynamic therapy (PDT) has been used to treat several types of cancer, and comprises intravascular administration of photosensitizer, uptake by cancer cells, and followed by irradiation of light of appropriate wavelength. Although PDT takes advantage of relative retention of photosensitizer by cancer cells, effective delivery of photosensitizing drugs is of great concern. Several delivery strategies have been employed in PDT. Photosensitizers can be delivered either by passive carriers such as liposomes, micelles, and polymeric particles, or by active targeting using cancer cell-directed ligands or antibodies. Although well-studied colloidal carriers effectively deliver photosensitizer to tumor cells, they are taken up by mononuclear phagocytic system. Delivery system using polymers is an attractive alternative to colloidal carriers, in which hydrophobic drugs are chemically or physically loaded to polymers. Though there are several steps to be solved, targeted delivery system utilizing receptors or antigens abundantly expressed on cancer cell theoretically provides a great deal of advantages over passive system. Selective uptake of photosensitizers by cancer cells may greatly enhance therapeutic efficacy as well as minimizing adverse effects resulting from accumulation in normal tissue. This review discusses various strategies for photosensitizer delivery that have been investigated to date.ope

Wnt-PLC-IP 3-Connexin-Ca 2+ axis maintains ependymal motile cilia in zebrafish spinal cord

Ependymal cells (ECs) are multiciliated neuroepithelial cells that line the ventricles of the brain and the central canal of the spinal cord (SC). How ependymal motile cilia are maintained remains largely unexplored. Here we show that zebrafish embryos deficient in Wnt signaling have defective motile cilia, yet harbor intact basal bodies. With respect to maintenance of ependymal motile cilia, plcδ3a is a target gene of Wnt signaling. Lack of Connexin43 (Cx43), especially its channel function, decreases motile cilia and intercellular Ca2+ wave (ICW) propagation. Genetic ablation of cx43 in zebrafish and mice diminished motile cilia. Finally, Cx43 is also expressed in ECs of the human SC. Taken together, our findings indicate that gap junction mediated ICWs play an important role in the maintenance of ependymal motile cilia, and suggest that the enhancement of functional gap junctions by pharmacological or genetic manipulations may be adopted to ameliorate motile ciliopathy.ope

Gene Expression Profiles in Pancreatic Intraepithelial Neoplasia Reflect the Effects of Hedgehog Signaling on Pancreatic Ductal Epithelial Cells

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EST vs EPBD for small CBD stones

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Oncogenic KRAS induces progenitor cell expansion and malignant transformation in zebrafish exocrine pancreas.

BACKGROUND & AIMS: Although the cell of origin for pancreatic cancer remains unknown, prior studies have suggested that pancreatic neoplasia may be initiated in progenitor-like cells. To examine the effects of oncogene activation within the pancreatic progenitor pool, we devised a system for real-time visualization of both normal and oncogenic KRAS-expressing pancreatic progenitor cells in living zebrafish embryos. METHODS: By using BAC transgenes under the regulation of ptf1a regulatory elements, we expressed either extended green fluorescent protein (eGFP) alone or eGFP fused to oncogenic KRAS in developing zebrafish pancreas. RESULTS: After their initial specification, normal eGFP-labeled pancreatic progenitor cells were observed to actively migrate away from the forming endodermal gut tube, and subsequently underwent characteristic exocrine differentiation. In contrast, pancreatic progenitor cells expressing oncogenic KRAS underwent normal specification and migration, but failed to differentiate. This block in differentiation resulted in the abnormal persistence of an undifferentiated progenitor pool, and was associated with the subsequent formation of invasive pancreatic cancer. These tumors showed several features in common with the human disease, including evidence of abnormal Hedgehog pathway activation. CONCLUSIONS: These results provide a unique view of the tumor-initiating effects of oncogenic KRAS in a living vertebrate organism, and suggest that zebrafish models of pancreatic cancer may prove useful in advancing our understanding of the human diseaseope

Analysis of Clinical Predictive Factors Affecting the Outcome of Second-Line Chemotherapy for Gemcitabine-Refractory Advanced Pancreatic Cancer

Background/Aims: The benefit of second-line chemotherapy (SL) after failed first-line chemotherapy (FL) in patients with advanced pancreatic cancer has not yet been established. We evaluated the clinical characteristics affecting the benefits of SL compared to best supportive care (BSC), identified the prognostic factors, and ultimately devised a model of clinical parameters to assist in making decision between SL and BSC after the failure of gemcitabine-based FL. Methods: The records of patients who received gemcitabinebased FL for advanced pancreatic cancer at Yonsei University Hospital between January 2010 and December 2015 were retrospectively reviewed. Significant clinical parameters were assessed for their potential as predictive factors. Results: SL patients received a longer duration of FL compared with BSC patients with median duration being 16.0 weeks (range, 8.0 to 26.0 weeks) and 8.0 weeks (range, 4.0 to 16.0 weeks), respectively (p<0.001). When the SL group was stratified by their modified overall survival (mOS) (longer and shorter than 6 months), we found significant differences for several clinical factors, namely, metastasis to the peritoneum (p<0.001), number of metastases (p<0.001), thrombotic events (p=0.003), and level of carbohydrate antigen 19-9 (CA19- 9; p=0.011). In multivariate analysis, more than one site of metastasis, occurrence of thrombotic event during FL, and a CA19-9 level above 90 U/mL were significant independent prognostic factors for mOS in the SL group (p<0.05). When an attempt was made to devise a prognostic nomogram, Harrell's C-index of the final prognosis prediction model was 0.62. Conclusions: SL may be beneficial for patients without peritoneal metastasis or thrombotic events who have a single metastasis and a level of CA19-9 less than 90 U/mL. This prognostic nomogram can be used to predict mOS before the administration of SL after the failure of gemcitabinebased FL.ope

Systemic Chemotherapy in Advanced Pancreatic Cancer

Pancreatic cancer remains one of the most lethal cancers. These patients often have multiple symptoms, and integrated supportive care is critical in helping them remain well for as long as possible. Fluorouracil-based chemotherapy is known to improve overall survival (OS) by approximately 3 months, compared to the best supportive care alone. A 1997 study comparing gemcitabine and fluorouracil treatment of advanced pancreatic cancer patients showed an improvement in OS of 1 month in patients receiving gemcitabine. Over the next 10 years, multiple randomized studies compared singleagent gemcitabine with combination chemotherapy and showed no effective survival improvement. However, the addition of erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, was associated with a significant improvement in OS of approximately 2 weeks. However, adoption of this regimen has not been widespread because of its limited effect and added toxicity. Two clinical trials have recently prolonged OS in advanced pancreatic cancer patients by almost 1 year. The first compared FOLFIRINOX with gemcitabine alone, and was associated with a significant improvement in median survival. The second compared gemcitabine and nabpaclitaxel with gemcitabine alone, and was associated with improvements in OS. At present, these regimens are considered standard treatment for patients with good performance statuses.ope

The Role of Endoscopy in Diagnosis and Treatment of Ampullary Tumor

Tumors of the major duodenal papilla, also known as ampullary tumor, are rare with an approximate 5% incidence of all gastrointestinal neoplasm. These tumors seem to be detected more frequently with increasing performance of upper endoscopic examination and endoscopic retrograde cholangiopancreatography (ERCP). Adenoma, most common benign disease of ampullary tumor, is very important because of its potential to undergo malignant transformation to ampullary cancer. Especially, endoscopic ultrasound or transpapillary intraductal ultrasonography can provide more detailed and accurate information on the extent of ampullary tumors and proper treatment should be done after diagnosis. Considering perioperative morbidity and mortality of surgical resection, endoscopic papillectomy is regarded as a curative treatment of ampullary adenoma. However, the indication of the procedure is very strict and there are various complications related to the procedure. Therefore, it is important to understand the role of endoscopy in diagnosis and treatment of ampullary tumor. In this review, the diagnostic role of endoscopy for ampullary tumor and the treatment method of endoscopic papillectomy will be discussed.ope